Galactofuranose (Galf) residues have been implicated in the virulence or viability of many microbes, including mycobacteria. The goal of the proposed research is to understand the mechanisms underlying Gacad lf residue incorporation into the mycobacterial cell wall. We shall investigate the structure and catalytic mechanism of a biology, microbiology, and chemical biology. and ideas from organic chemistry, glycobiology, carbohydrate chemistry, chemical enzymology, structural of UGM that can be used as probes of cell wall biosynthesis. In pursuing these Aims, we shall employ methods the generation of inhibitors of this essential enzyme. Aim 2 is to generate potent and cell-permeable inhibitors chemistry of the flavoenzymes, provide insight into the chemistry underlying cell wall biosynthesis, and guide flavoenzyme UGM. Elucidating the catalytic mechanism UGM will enhance our understanding of the diverse UGM). The two Specific Aims of this application follow. Aim 1 is to understand the mechanism of the key enzyme in this process: the flavoenzyme uridine-5'-diphosphate (UDP)-galactopyranose mutase (Glf or 'C; phi 1141 mfg coo ID0 v[unreadable][unreadable] centh+ Significance: The results of the proposed research will provide new insights into the assembly of the galactan polymer, an essential component of the mycobacterial cell wall. This knowledge will be applied to develop small molecules that block mycobacterial cell growth. Such agents wijI serve as valuable probes of mycobacterial cell wall biosynthesis and as leads for the development of new antimycobacterial drugs. ,-t (L) O''